(Z)-methyl 3-(3,4-bis(difluoromethoxy)phenyl)-2-(tert-butoxycarbonylamino)acrylate | 1373754-40-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (Z)-methyl 3-(3,4-bis(difluoromethoxy)phenyl)-2-(tert-butoxycarbonylamino)acrylate
• 英文别名: methyl (Z)-3-[3,4-bis(difluoromethoxy)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]prop-2-enoate
• CAS: 1373754-40-5
• 化学式: C₁₇H₁₉F₄NO₆
• 分子量: 409.335
• InChiKey: AXQRCPOLVMWNOO-YFHOEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (Z)-methyl 3-(3,4-bis(difluoromethoxy)phenyl)-2-(tert-butoxycarbonylamino)acrylate 在 (1R,2S)-2-tert-butyl-1-((1R,2S)-2-tertbutyl-2,3-dihydro-1H-isophosphindol-1-yl)-2,3-dihydro-1H-isophosphindole 、 isobutyl chloroformate 、 氢气 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 7.5h， 生成 (S)-tert-butyl 1-(3,4-bis(difluoromethoxy)phenyl)-4-diazo-3-oxobutan-2-ylcarbamate
  参考文献：
  名称：

  Design and Preparation of a Potent Series of Hydroxyethylamine Containing β-Secretase Inhibitors That Demonstrate Robust Reduction of Central β-Amyloid

  摘要：

  A series of potent hydroxyethyl amine (HEA) derived inhibitors of beta-site APP cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a series of benzodioxolane analogues that possessed improved metabolic stability and increased oral bioavailability. Subsequent efforts focused on improving CNS exposure by limiting susceptibility to Pgp-mediated efflux and identified an inhibitor which demonstrated robust and sustained reduction of CNS beta-amyloid (A beta) in Sprague-Dawley rats following oral administration.

  DOI：

  10.1021/jm300119p
• 作为产物：
  描述：

  3,4-双(二氟甲氧基)苯甲醛 、 trimethyl 2-(tert-butoxycarbonylamino)phosphonoacetate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 2.33h， 以93.9%的产率得到(Z)-methyl 3-(3,4-bis(difluoromethoxy)phenyl)-2-(tert-butoxycarbonylamino)acrylate
  参考文献：
  名称：

  Design and Preparation of a Potent Series of Hydroxyethylamine Containing β-Secretase Inhibitors That Demonstrate Robust Reduction of Central β-Amyloid

  摘要：

  A series of potent hydroxyethyl amine (HEA) derived inhibitors of beta-site APP cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a series of benzodioxolane analogues that possessed improved metabolic stability and increased oral bioavailability. Subsequent efforts focused on improving CNS exposure by limiting susceptibility to Pgp-mediated efflux and identified an inhibitor which demonstrated robust and sustained reduction of CNS beta-amyloid (A beta) in Sprague-Dawley rats following oral administration.

  DOI：

  10.1021/jm300119p